The conventional tissue perfusion measuring method ‘laser Doppler imaging’ is a method of measuring the degree of scattering of laser light depending on the speed of blood flow in a skin surface, but has a shortcoming in that it is unsuitable for a method of measuring variation in the state in which blood flow is low because sensitivity is low when blood flow rate decreases to less than 20% of the normal of the blood flow rate.
Another conventional blood vessel imaging method ‘X-ray blood vessel imaging (X-ray angiography)’ shows X-ray images using a blood vessel contrast agent. However, it is a structural imaging technique that shows the configuration of the internal diameters of blood vessels, rather than the actual flow of blood (Helisch, A., Wagner, S., Khan, N., Drinane, M., Wolfram, S., Heil, M., Ziegelhoeffer, T., Brandt, U., Pearlman, J. D., Swartz, H. M. & Schaper, W. (2006) Arterioscler. Thromb. Vasc. Biol., 26: 520-526). Accordingly, it is currently impossible to clinically measure the precise rate of tissue perfusion using this method.
The safety of a conventional blood vessel imaging method using indocyanine green (ICG angiography) has already been verified (Sekimoto, M., Fukui, M. & Fujita, K. (1997) Anaesthesia 52: 1166-1172), and the method has been clinically used for the detection of the formation of blood vessels in grafted skin (Holm, C., Mayr, M., Hofter, E., Becker, A., Pfeiffer, U. J. & Muhlbauer, W. (2002) Br. J. Plast. Surg. 55: 635-644) and the measurement of newly created blood vessels in a diabetic patient's eyeballs (Costa, R. A., Calucci, D., Teixeira, L. F., Cardillo, J. A. & Bonomo, P. P. (2003) Am. J. Opthalmol. 135: 857-866). ICG receives near infrared rays, having wavelengths ranging from 750-790 nm, and radiates near infrared rays, having longer wavelengths ranging from 800 to 850 nm, and the radiated near infrared rays can be measured using a CCD camera or a spectrometer. Near infrared rays have high penetration power, and thus they can penetrate several centimeters deep into tissue and don't scatter much, with the result that they are the object of extensive research towards human body imaging technology (Morgan, N. Y., English, S., Chen, W., Chernomordik, V., Russo, A., Smith, P. D. & Gandjbakhche, A. (2005) Acad. Radiol. 12: 313-323). This method is also used as a technique for structural blood vessel imaging. This method is used for the test of the permeability of newly created blood vessels in a diabetic patient's eyeballs, not for the measurement of tissue perfusion.
The above method is used for an ‘ICG elimination test’ as well as the above purpose. When ICG is injected into a vein, ICG is attached to protein in a blood vessel, such as albumin, and is rapidly spread into the body via blood vessels. When it is transferred to the liver, it is separated from protein and discharged in the form of bile and excreted from the body finally while the protein is degraded. As a result, the concentration of ICG is rapidly reduced in the blood vessels, so that the intensity of ICG fluorescence signals is reduced to half of the intensity of initial ICG fluorescence signals 4 to 6 minutes later, and is then diminished and deviates from an accurate measurement range. One use of the ‘ICG dynamics’, in which ICG is rapidly eliminated by the liver, is a liver function test (Sinyoung Kim, et al., (2003) Kor. J. Lab. Med., 23: 88-91), but the ICG dynamics has been known to have shortcomings when applied to in vivo imaging (Sekimoto, M., Fukui, M. & Fujita, K. (1997) Anaesthesia 52: 1166-1172).Accordingly, the present inventors have completed the present invention through the ascertainment of the fact that accurate measurement can be conducted in a wide range from a perfusion rate decreased to less than 10% of that of normal perfusion to a perfusion rate increased to greater than that of normal perfusion using the ICG dynamics in the living body.